SALM4/LRFN3: Proteins and Enzymes

Synaptic adhesion-like molecule 4 (SALM4; also leucine-rich repeat and fibronectin type-III domain-containing protein 3 (Lrfn3) is an approximately 90 kDa member of the Lrfn family of type I transmembrane glycoproteins. Human SALM4 is synthesized as a 628 amino acid (aa) precursor that contains a 16 aa signal sequence, a 523 aa extracellular domain (ECD), a 21 aa transmembrane region, and a 68 aa cytoplasmic region. The ECD consists of six leucine-rich repeats (LRR), an IgC2-like domain, and a fibronectin type-III domain, tandemly aligned in that order. In addition, there are five potential sites for N-linked glycosylation. SALM4 and SALM5 lack a C-terminal intracellular PDZ binding domain, which is conserved among SALMs 1-3. Mature human SALM4 shares 96% aa sequence identity with mature mouse SALM4. Northern blot analysis showed that in mice, SALM4 is strongly expressed in the adult brain and is also present in the adult gastrointestinal tract and kidneys. It is distributed throughout the neuron, including the growth cone. In the developing mouse embryo, a temporal expression profile blot revealed a general increment of expression around E10.5, with weak expression detected before E10.5. SALM4, like the other SALMs, promotes neurite outgrowth. Specifically, the SALMs modify total outgrowth and neurite branching.